Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The somatostatin (SST) gene was analyzed to detect possible molecular variations in subjects with familial isolated growth hormone deficiency type I (IGHD I). No gross alterations in restriction fragments were observed with 18 used enzymes. The association with two RFLPs closely linked to the SST gene was also negative, adding weight to the evidence that the SST gene is not involved in the etiology of IGHD I. The nucleotide variability of a 23-kb DNA segment containing the SST gene and its flanking sequences was studied by restriction analysis of a sample of 19 Italians. The data suggest that approximately 1 in 400 bp is variant in this region.
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PMID:DNA restriction fragment analysis of the somatostatin gene in familial isolated growth hormone deficiency type I. 134 99

To study the site of lesions in idiopathic growth hormone (GH) deficiency (IGHD), growth hormone releasing hormone (GHRH) was administered sequentially for 3 days to 19 patients with IGHD, 3 patients with GH deficiency (GHD) secondary to hypothalamic tumors, and 7 normal short children (NSC). GHRH (100 micrograms) was injected as a bolus on days 1 and 3, and was infused over 60 min on day 2. Of 19 patients with IGHD, 6 showed an improved GH response (group A), 5 a decreased response (group B) and the remaining 8 an unchanged response (group C) to sequential administration of GHRH. The response was unchanged in patients with secondary GHD or NSC. There was no significant correlation between the patterns of GH response and the findings on pituitary MR images or the delivery state at birth in IGHD patients. Ten patients with IGHD (4 of group A; 3 each of groups B & C) and 2 NSC showed much greater GH responses to arginine (0.5 g/kg i.v. for 30 min) injected with preceding GHRH than to arginine injected without preceding GHRH. These results indicate that hypothalamic lesions were primarily responsible for GH deficiency in about 60% of the patients with IGHD (groups A and B), and group C might have more severe hypothalamo-pituitary damages than the other groups. Hypothalamic somatostatin neurons seems to be functioning to a degree even in severe IGHD patients.
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PMID:Plasma GH response to the sequential 3 day administrations of GHRH followed by arginine infusion in patients with idiopathic GH deficiency and normal short children. 823 47

Autosomal dominant GH deficiency type II (IGHDII) is often associated with mutations in the human GH gene (GH1) that give rise to products lacking exon-3 ((Deltaexon3)hGH). In the heterozygous state, these act as dominant negative mutations that prevent the release of human pituitary GH (hGH). To determine the mechanisms of these dominant negative effects, we used a combination of transgenic and morphological approaches in both in vitro and in vivo models. Rat GC cell lines were generated expressing either wild-type GH1 (WT-hGH-GC) or a genomic GH1 sequence containing a G->A transition at the donor splice site of IVS3 ((Deltaexon3)hGH-GC). WT-hGH-GC cells grew normally and produced equivalent amounts of human and rGH packaged in dense-cored secretory vesicles (SVs). In contrast, (Deltaexon3)hGH-GC cells showed few SVs but accumulated secretory product in amorphous cytoplasmic aggregates. They produced much less rGH and grew more slowly than WT-hGH-GC cells. When cotransfected with an enhanced green fluorescent protein construct (GH-eGFP), which copackages with GH in SVs, WT-hGH-GC cells showed normal electron microscopy morphology and SV movements, tracked with total internal reflectance fluorescence microscopy. In contrast, coexpression of (Deltaexon3)hGH with GH-eGFP abolished the vesicular targeting of GH-eGFP, which instead accumulated in static aggregates. Transgenic mice expressing (Deltaexon3)hGH in somatotrophs showed an IGHD-II phenotype with mild to severe pituitary hypoplasia and dwarfism, evident at weaning in the most severely affected lines. Hypothalamic GHRH expression was up-regulated and somatostatin expression reduced in (Deltaexon3)hGH transgenic mice, consistent with their profound GHD. Few SVs were detectable in the residual pituitary somatotrophs in (Deltaexon3)hGH transgenic mice, and these cells showed grossly abnormal morphology. A low copy number transgenic line showed a mild effect relatively specific for GH, whereas two severely affected lines with higher transgene copy numbers showed early onset, widespread pituitary damage, macrophage invasion, and multiple hormone deficiencies. These new in vitro and in vivo models shed new light on the cellular mechanisms involved in IGHDII, as well as its phenotypic consequences in vivo.
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PMID:Autosomal dominant growth hormone deficiency disrupts secretory vesicles in vitro and in vivo in transgenic mice. 1253 35